Yao Minglan, Zhang Cai, Li Sujuan, Tian Anran, Liang Furong, Luo Xiaoping
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, Hubei Province 430030, P. R. China.
Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases, No. 1095, Jiefang Avenue, Wuhan, Hubei Province 430030, P. R. China.
Hum Mol Genet. 2025 Sep 19;34(19):1665-1673. doi: 10.1093/hmg/ddaf128.
SPONASTRIME dysplasia is a rare genetic disorder characterized by short stature, facial abnormalities, vertebral issues, and bone striations, caused by recessive mutations in the TONSL gene. We reported a 6-year-old boy with characteristic clinical features of SPONASTRIME dysplasia, accompanied by neutropenia. Genetic analysis revealed biallelic variants in TONSL: mother-inherited c.1289del (p.Gln430ArgfsTer13) and father-inherited c.1961G > C (p.Arg654Pro), both of which were previously unreported. We predicted the c.1289del (p.Gln430ArgfsTer13) variant as likely pathogenic in silico analysis, while the c.1961G > C (p.Arg654Pro) variant as uncertain pathogenicity in silico analysis, and the pathogenicity was confirmed by functional studies in transfected HEK 293 T cells. Six-month growth hormone therapy was administered to the patient after confirmed diagnosis, with limited improvement. These findings have important implications for the diagnosis and treatment of the disease.
